Benefits and risks of minocycline in rheumatoid arthritis

Rheumatoid arthritis is a chronic inflammatory disease affecting about 1% of the adult population. The pathophysiology of rheumatoid arthritis remains incompletely understood. An infectious aetiology of the disease has long been postulated, but not proved. Despite insufficient evidence for the infectious nature of this disorder, several antibacterials, such as sulfa compounds, tetracyclines and rifampicin, have been investigated in the treatment of rheumatoid arthritis. In the last few years, minocycline, a semi-synthetic derivative of tetracycline, has been extensively studied as a therapeutic agent for rheumatoid arthritis. The antirheumatic effect of minocycline can be related to its immunomodulatory and anti-inflammatory, rather than to its antibacterial properties. Its efficacy in rheumatoid arthritis has been reported in 2 open trials and in 3 double-blind controlled studies. The first 2 double-blind studies, 1 in The Netherlands and 1 in the US, were performed in patients with advanced disease. Both studies showed a modest, but statistically significant improvement in the clinical parameters of disease activity and in the erythrocyte sedimentation rate in the minocycline-treated patients. The US study also reported that patients in the minocycline group developed fewer erosions than those in the placebo group. This finding supports the role of minocycline as a disease modifying agent. The common adverse effects of minocycline reported in these 2 studies included gastrointestinal adverse effects, dizziness, rash and headaches. Less common adverse effects were intracranial hypertension, pneumonitis, persistent skin and mucosal hyperpigmentation, lupus-like syndrome and acute hepatic injury. The third double-blind study enrolled only seropositive rheumatoid arthritis patients with early disease (less than 1 year duration), and showed very encouraging results of significant improvement in the disease activity parameters in the minocycline treated group of patients. The same authors later reported that about half of these patients were in or near remission after 3 years of follow up. No adverse effects were reported in this study. Summarising the data of these 3 double-blind studies, we may conclude that minocycline may be beneficial in patients with rheumatoid arthritis, especially when given early in the disease course or in patients with a mild disease.